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In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells

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In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells. / El-Heliebi, Amin; Hille, Claudia; Laxman, Navya; Svedlund, Jessica; Haudum, Christoph; Ercan, Erkan; Kroneis, Thomas; Chen, Shukun; Smolle, Maria; Rossmann, Christopher; Krzywkowski, Tomasz; Ahlford, Annika; Darai, Evangelia; von Amsberg, Gunhild; Alsdorf, Winfried; König, Frank; Löhr, Matthias; de Kruijff, Inge; Riethdorf, Sabine; Gorges, Tobias M; Pantel, Klaus; Bauernhofer, Thomas; Nilsson, Mats; Sedlmayr, Peter.

in: CLIN CHEM, Jahrgang 64, Nr. 3, 03.2018, S. 536-546.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

El-Heliebi, A, Hille, C, Laxman, N, Svedlund, J, Haudum, C, Ercan, E, Kroneis, T, Chen, S, Smolle, M, Rossmann, C, Krzywkowski, T, Ahlford, A, Darai, E, von Amsberg, G, Alsdorf, W, König, F, Löhr, M, de Kruijff, I, Riethdorf, S, Gorges, TM, Pantel, K, Bauernhofer, T, Nilsson, M & Sedlmayr, P 2018, 'In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells', CLIN CHEM, Jg. 64, Nr. 3, S. 536-546. https://doi.org/10.1373/clinchem.2017.281295

APA

El-Heliebi, A., Hille, C., Laxman, N., Svedlund, J., Haudum, C., Ercan, E., Kroneis, T., Chen, S., Smolle, M., Rossmann, C., Krzywkowski, T., Ahlford, A., Darai, E., von Amsberg, G., Alsdorf, W., König, F., Löhr, M., de Kruijff, I., Riethdorf, S., ... Sedlmayr, P. (2018). In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells. CLIN CHEM, 64(3), 536-546. https://doi.org/10.1373/clinchem.2017.281295

Vancouver

El-Heliebi A, Hille C, Laxman N, Svedlund J, Haudum C, Ercan E et al. In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells. CLIN CHEM. 2018 Mär;64(3):536-546. https://doi.org/10.1373/clinchem.2017.281295

Bibtex

@article{6a11db86331b493dae468d64c7936476,
title = "In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells",
abstract = "BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.",
keywords = "Journal Article",
author = "Amin El-Heliebi and Claudia Hille and Navya Laxman and Jessica Svedlund and Christoph Haudum and Erkan Ercan and Thomas Kroneis and Shukun Chen and Maria Smolle and Christopher Rossmann and Tomasz Krzywkowski and Annika Ahlford and Evangelia Darai and {von Amsberg}, Gunhild and Winfried Alsdorf and Frank K{\"o}nig and Matthias L{\"o}hr and {de Kruijff}, Inge and Sabine Riethdorf and Gorges, {Tobias M} and Klaus Pantel and Thomas Bauernhofer and Mats Nilsson and Peter Sedlmayr",
note = "{\textcopyright} 2018 American Association for Clinical Chemistry.",
year = "2018",
month = mar,
doi = "10.1373/clinchem.2017.281295",
language = "English",
volume = "64",
pages = "536--546",
journal = "CLIN CHEM",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells

AU - El-Heliebi, Amin

AU - Hille, Claudia

AU - Laxman, Navya

AU - Svedlund, Jessica

AU - Haudum, Christoph

AU - Ercan, Erkan

AU - Kroneis, Thomas

AU - Chen, Shukun

AU - Smolle, Maria

AU - Rossmann, Christopher

AU - Krzywkowski, Tomasz

AU - Ahlford, Annika

AU - Darai, Evangelia

AU - von Amsberg, Gunhild

AU - Alsdorf, Winfried

AU - König, Frank

AU - Löhr, Matthias

AU - de Kruijff, Inge

AU - Riethdorf, Sabine

AU - Gorges, Tobias M

AU - Pantel, Klaus

AU - Bauernhofer, Thomas

AU - Nilsson, Mats

AU - Sedlmayr, Peter

N1 - © 2018 American Association for Clinical Chemistry.

PY - 2018/3

Y1 - 2018/3

N2 - BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.

AB - BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.

KW - Journal Article

U2 - 10.1373/clinchem.2017.281295

DO - 10.1373/clinchem.2017.281295

M3 - SCORING: Journal article

C2 - 29301749

VL - 64

SP - 536

EP - 546

JO - CLIN CHEM

JF - CLIN CHEM

SN - 0009-9147

IS - 3

ER -